Chronic myelomonocytic leukemia (CMML) and juvenile myelomonocytic leukemia (JMML) are clonal hematologic malignancies characterized by myelodysplastic syndromes (MDS) and myeloproliferative diseases (MPD). CMML and JMML are associated with mutations at carcinogenic sites in genes involved in RAS/MAPK signaling, and 25% to 40% of patients suffering from CMML/JMML have somatic mutations in NRAS gene. It has been reported that a mouse carrying an endogenous mutation of the Nras allele will suffer from a CMML-like disease, which disease has a long latency. It has also been reported that frequent associations between MDS/MPN diseases and the functional disorders of bone marrow (BM) microenvironment have been shown in human patients and animal models that are suffering from CMML/JMML. Aplastic anemia (AA) is a disease mainly characterized by decrease of whole blood cells caused by the failure in hematopoietic function of bone marrow, which is caused in turn by bone marrow hematopoietic stem cell deficiencies, impaired hematopoietic micro-environment and immune mechanism changes due to a variety of factors. The bone marrow microenvironment is a complex network structure with multiple functions, consisting of several types of cells including mesenchymal stromal cells (MSCs), endosteal osteoblasts (OBs), endothelial cells and other rare cell types. The MSCs can be isolated and proliferate in vitro. MSCs are precursor cells of bone marrow stromal cells and account for 0.01% to 0.001% of bone marrow mononuclear cells, equivalent to 1% of the number of HSCs. MSCs can differentiate into osteoblasts, chondrocytes, adipocytes, myocytes, pericytes, reticular fibroblasts and nerve cells among other types under different induction conditions.
At present, MSCs are commonly used in the treatment of systemic graft versus host disease (GVHD) and can improve wound healing and promote the recovery of lung damage, kidney damage and myocardial damage. However, the response to MSCs is not always desirable, and for example, it is known to be affected by the inflammatory state in patients. In addition, MSCs are pluripotent cells and can differentiate into adipocytes, osteoblasts, chondrocytes, myoblasts and/or neuron-like cells after being injected into recipient host. Therefore, it is difficult to predict the exact results of injecting the MSCs into BM microenvironment, such as effects of MSCs injection on the recovery of normal hematopoietic functions, the inhibition of disease progression and other aspects.
At present, the methods for treating hematologic malignancies mainly include chemotherapy, radiotherapy and combined hematopoietic stem cell transplantation. However, the treatment methods described above are accompanied by, in addition to tumor recurrence, varying degrees of side effects including severe damage to non-tumor, healthy cells, especially to germ cells, and graft versus host disease (GVHD) and the like, which seriously affect the life quality of patients. Therefore, there is an urgent need for such treatment methods that can effectively treat the hematologic tumors but have little or even no side effects on patients. The bone marrow microenvironment in patients suffering from hematologic malignancies is usually destructed by the tumor, and thus the normal hematopoiesis of the bone marrow is reduced, or even to failure. In turn, dysfunction/depletion of the bone marrow mesenchymal microenvironment plays a positive role in promoting the progression of pathological deterioration of hematologic malignancies including leukemia, and aplastic anemia. So far, there is no effective way to solve problems in the remolding of pathological bone marrow microenvironment. Therefore, it is very important for the remolding of bone marrow microenvironment under pathological condition and for the remission and treatment of hematologic malignancies to provide a method for remolding bone marrow microenvironment effectively.